In a finding sure to cause many cardiac patients some old-fashioned
heartburn, researchers report that a commonly prescribed class of
acid-blocking drugs interferes with an anticlotting medication routinely
given to heart patients discharged from the hospital. The study, coupled
with earlier reports that have led to a stern warning from the U.S. Food
and Drug Administration about mixing the drugs, might change
doctors' c practices.

"A lot of us just prescribe things out of habit," says
study coauthor E Michael Ho, a car diologist at the Denver Veterans
Affairs Medical Center. "My hope is that this study makes
physicians think twice."

The new report, in the March 4 Journal of the American Medical
Association, suggests that proton pump inhibitors neutralize more than
stomach acid.

PPIs seem to inhibit the blood thinner clopidogrel, marketed as
Plavix. Clopidogrel is a standard antiplatelet drug for people recently
treated for heart problems. It doesn't actually thin the blood, but
it does discourage platelets from forming clots. That's a boon for
people with clogged coronary arteries that have been recently reopened.

Because clopidogrel can irritate the stomach in some patients, many
doctors also prescribe a PPI such as Prilosec, Nexium, Aciphex, Prevacid
or Protonix.

Ho and his colleagues reviewed the medical records of 8,205 people,
nearly all men, who were prescribed clopidogrel upon discharge from
Veterans Affairs hospitals between October 2003 and January 2006. All
had been treated for a heart attack or other serious heart problem.

The records show that most were also prescribed a PPI upon
discharge. After an average follow-up of 17 months, those getting both
drugs were nearly twice as likely to have been rehospitalized for a
heart problem as those getting clopidogrel but not a PPI. Also, people
getting both drugs were about 50 percent more likely to require a
procedure to reopen a coronary artery.

The scientists accounted for differences in health between the
groups including diabetes, lung disease and dementia. And after omitting
anyone with previous stomach or intestinal bleeding those getting both
drugs were still more likely to experience a serious heart problem.

Clopidogrel must be activated by enzymes in the liver to work. But
PPIs seem to shut off these enzymes and interfere with clopidogrel, says
Robert S. Epstein, an epidemiologist and chief medical officer at Medco,
a pharmacy benefits management company based in Franklin Lakes, N.J.

Non-PPI heartburn drugs that include Zantac, Pepcid, Axid and
Tagamet didn't have this effect in previous research and showed
little correlation in this one.

"This is a very important paper," says Epstein.
"They did a very good job of weeding out--and adjusting
for--differences between the groups."

Epstein and his colleagues also recently found depleted clopidogrel
action when it was coupled with a PPI, as did a Canadian team in a
separate study. Based on a series of findings, the FDA issued a warning
in January that "patients taking clopidogrel should consult with
their health care provider if they are currently taking or considering
taking a PPI."

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